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  • 1
    Electronic Resource
    Electronic Resource
    Dose-intense therapy with etoposide, ifosfamide, cisplatin, and epirubicin (VIP-E) in 107 consecutive patients with limited- and extensive-stage non-small-cell lung cancer (1997)
    Springer
    Annals of oncology 8 (1997), S. 57-64 
    Details
    ISSN: 1569-8041
    Keywords: chemotherapy ; hematopoietic growth-factor support ; high-dose chemotherapy ; non-small-cell lung cancer ; peripheral blood stem cell transplantation ; treatment toxicity and mortality
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: We conducted a phase I/II trial to assess the feasibilityand activity of combination chemotherapy with etoposide, ifosfamide,cisplatin, and epirubicin in limited-stage (LS, stage I–IIIB) andextensive-stage (ES, stage IV) non-small-cell lung cancer (NSCLC). End-pointswere treatment-related morbidity and mortality, response rate, duration ofresponse, and survival. Patients and methods: Chemotherapy followed by granulocytecolony-stimulating factor was given at a dose of etoposide (500mg/m2), ifosfamide (4000 mg/m2), cisplatin (50mg/m2), and epirubicin (50 mg/m2) (VIP-E) to107 patients with NSCLC. Twenty-five patients with qualifying responsesproceeded to high-dose chemotherapy with autologous peripheral blood stem celltransplantation after etoposide (1500 mg/m2), ifosfamide(12,000 mg/m2), carboplatin (750 mg/m2) andepirubicin (150 mg/m2) (VIC-E) conditioning. Results of conventional-dose VIP-E: 35 of 102 (34%) evaluablepatients responded (2 CR's, 33 PR's), 33/102 patients (33%) showed nochange (NC); the remainder of patients progressed with therapy (PD). Objectiveresponse rate was 68% (4% CR, 64% PR) in LS-NSCLC and23% (1.4% CR, 21.4% PR) in ES-NSCLC. Median duration ofsurvival was 13 months in LS-NSCLC and 5.5 months in ES-NSCLC. Two-yearsurvival was 26% in LS and 2% in ES-NSCLC. Results of high-dose VIC-E: 23 of 24 evaluable patients improved ormaintained prior responses (92%), 1 patient showed NC. Treatmentmortality was 4%. Median duration of survival was 17 months in LS-NSCLCand 10 months in ES-NSCLC. Two-year survival was 30% in LS and8% in ES-NSCLC. Conclusion: Response-rates and survival after conventional-dose VIP-Echemotherapy are comparable to other published trials of combinationchemotherapy in NSCLC. Toxicity and mortality is acceptable in limited stage,but unacceptably high in extensive stage NSCLC. Although better response-rateswere achieved in the high-dose arm, they did not translate into improvedsurvival. Most stage IV NSCLC-patients will neither benefit from VIP-Econventional dose, nor from VIC-E high dose chemotherapy. Whether selectedLS-patients with partial or complete responses to VIP-E induction chemotherapycould benefit from dose intensification in an adjuvant or neo-adjuvant settingremains to be determined.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008209713568
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  • 2
    Electronic Resource
    Electronic Resource
    Dose-intense therapy with etoposide, ifosfamide, cisplatin, and epirubicin (VIP-E) in 100 consecutive patients with limited- and extensive-disease small-cell lung cancer (1997)
    Springer
    Annals of oncology 8 (1997), S. 49-56 
    Details
    ISSN: 1569-8041
    Keywords: chemotherapy ; hematopoietic growth-factor support ; high-dose chemotherapy ; peripheral blood stem cell transplantation ; small-cell lung cancer ; treatment toxicity and mortality
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: We conducted a phase I/II trial to assess the feasibilityand activity of VIP-E chemotherapy in small-cell lung cancer. End-points weretreatment-related morbidity and mortality, response to treatment, duration ofresponse, and survival. Patients and methods: Two cycles of combination chemotherapy followedby granulocyte colony-stimulating factor (G-CSF) were given at a dose ofetoposide (500 mg/m2), ifosfamide (4000mg/m2), cisplatin (50 mg/m2), and epirubicin(50 mg/m2) to 100 consecutive patients with SCLC. Thirtypatients (19 with LD, and 11 with ED SCLC) proceeded to VIC-E high-dosechemotherapy with autologous peripheral blood stem cell transplantation(PBSCT) at a cumulative dose of etoposide 1500 mg/m2,ifosfamide 12,000 mg/m2, carboplatin 750 mg/m2and epirubicin 150 mg/m2 (VIC-E). Surgical resection ofprimary tumor was attempted at the earliest feasible point. Thoracicirradiation was given after completion of chemotherapy. Results of conventional-dose VIP-E: 97 patients were evaluable forresponse. Objective response rate was 81% in LD-SCLC (33% CR,48% PR; excluding patients in surgical CR) and 77% in ED-SCLC(18% CR, 58% PR). Treatment mortality was 2%. Mediansurvival was 19 months in LD-SCLC and 6 months in ED-SCLC. Two-year survivalwas 36% in LD and 0% in ED SCLC. Results of high-dose VIC-E: All 30 patients improved on or maintainedprior responses. Four patients (13%) died of treatment-relatedcomplications. Median survival was 26 months in LD-SCLC and 8 months inED-SCLC. Two-year survival was 53% in LD and 9% in ED SCLC. Conclusion: VIP-E chemotherapy is an effective induction therapy forSCLC. Compared with traditional protocols such as ACO orcarboplatin/etoposide, response rates are slightly improved, while survivalis not different. In the LD SCLC subgroup, high-dose chemotherapy improvedresponse rates and survival, especially for patients in surgical CR prior tohigh-dose therapy. In ED SCLC, however, higher response-rates did nottranslate into improved survival. Selected LD-SCLC patients with good partialor complete remissions after prior therapy may benefit from HDC and PBSCT.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008232329498
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  • 3
    Electronic Resource
    Electronic Resource
    Expression of the Fas antigen on primary human leukemia cells (1995)
    Springer
    Annals of hematology 70 (1995), S. 15-17 
    Details
    ISSN: 1432-0584
    Keywords: Fas antigen ; Apoptosis ; Leukemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The antigen defined by the monoclonal antibody anti-Fas can mediate apoptosis, is associated with the receptor for tumor necrosis factor, and is expressed on a limited number of human tissues. In this study we analyzed the expression of Fas on primary human leukemic cells and on mononuclear cells from other hematologic disorders. A total of 95 samples of blood or bone marrow were studied by indirect immunofluorescence. These samples included the normal controls, 47 cases of acute myelogenous leukemia (AML), 11 cases of acute lymphoblastic leukemia (ALL), 21 cases of leukemic lymphoma, seven cases of chronic myelogenous leukemia (CML), five cases of plasma cell leukemia or multiple myeloma, and five cases of myelodysplastic or myeloproliferative syndromes. Normal controls were negative without exception. Among AML, 13/47 cases (28%) were positive; among ALL, 1/11 cases (9%) was positive; among leukemic lymphomas, 3/21 cases (14%) were positive. In a case of plasma cell leukemia which strongly expressed the Fas antigen, we demonstrated that the antibody mediates cell lysis, which was synergistically enhanced by the addition of rabbit complement. In patients with AML, Fas positivity had no obvious clinical relevance. Taken together, our results show that approximately 30% of cases of AML and occasionally other leukemias express the Fas antigens, whereas normal controls are negative in our test system. These findings may be useful in the treatment of refractory leukemias or may permit the purging of autologous transplants.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01715376
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  • 4
    Electronic Resource
    Electronic Resource
    Lymphokine activated killer cells (1989)
    Springer
    Annals of hematology 59 (1989), S. 375-384 
    Details
    ISSN: 1432-0584
    Keywords: Lymphokine activated killer cells ; Interleukin-2
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Various subpopulations of human leukocytes may be induced by lymphokines to exert cytotoxic activity. In man major histocompatibility complex non-restricted tumor cell lysis by interleukin-2 (IL-2) induced peripheral blood lymphocytes is attributed mainly to natural killer cells. These T cell receptor negative large granular lymphocytes are called lymphokine activated killer (LAK) cells. In order to explore the potential of LAK cells in tumor therapy, several clinical studies have been conducted, using IL-2 alone or in combination with ex vivo IL-2-activated peripheral blood lymphocytes. Objective responses have reproducibly been achieved only in renal cell carcinoma and malignant melanoma and were associated with considerable toxicity. In view of restricted efficacy and increasing doubts as to whether LAK cells indeed account for the in vivo observed responses, more recent strategies focus on tumor antigen specific cytotoxic T cells or tumor infiltrating lymphocytes. Successful translation of this approach into clinical practice, however, may be dependend on some basic problems of tumor immunology to be solved which were thought to be by-passed by the LAK cell approach.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00321208
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  • 5
    Electronic Resource
    Electronic Resource
    Expression of the Fas antigen on primary human leukemia cells (1995)
    Springer
    Annals of hematology 70 (1995), S. 15-17 
    Details
    ISSN: 1432-0584
    Keywords: Key words Fas antigen ; Apoptosis ; Leukemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary  The antigen defined by the monoclonal antibody anti-Fas can mediate apoptosis, is associated with the receptor for tumor necrosis factor, and is expressed on a limited number of human tissues. In this study we analyzed the expression of Fas on primary human leukemic cells and on mononuclear cells from other hematologic disorders. A total of 95 samples of blood or bone marrow were studied by indirect immunofluorescence. These samples included the normal controls, 47 cases of acute myelogenous leukemia (AML), 11 cases of acute lymphoblastic leukemia (ALL), 21 cases of leukemic lymphoma, seven cases of chronic myelogenous leukemia (CML), five cases of plasma cell leukemia or multiple myeloma, and five cases of myelodysplastic or myeloproliferative syndromes. Normal controls were negative without exception. Among AML, 13/47 cases (28%) were positive; among ALL, 1/11 cases (9%) was positive; among leukemic lymphomas, 3/21 cases (14%) were positive. In a case of plasma cell leukemia which strongly expressed the Fas antigen, we demonstrated that the antibody mediates cell lysis, which was synergistically enhanced by the addition of rabbit complement. In patients with AML, Fas positivity had no obvious clinical relevance. Taken together, our results show that approximately 30% of cases of AML and occasionally other leukemias express the Fas antigens, whereas normal controls are negative in our test system. These findings may be useful in the treatment of refractory leukemias or may permit the purging of autologous transplants.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01715376
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  • 6
    Electronic Resource
    Electronic Resource
    Leukocytoclastic vasculitis and long-term remission in a patient with secondary AML and post-remission treatment with low-dose interleukin-2 (1995)
    Springer
    Annals of hematology 70 (1995), S. 227-230 
    Details
    ISSN: 1432-0584
    Keywords: Interleukin-2 ; Acute myeloid leukemia ; Leukocytoclastic vasculitis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Interleukin-2 (IL-2) has been licensed for the treatment of renal cell carcinoma and is currently being evaluated as a therapeutic agent in hematological malignancies. It is associated with a variety of side effects due to induction of a nonspecific inflammatory response. However, phenomena of autoimmunity have also been reported. Here we describe a patient with secondary acute myeloid leukemia who developed a leukocytoclastic vasculitis during long-term post-remission treatment with very low doses of IL-2.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01700380
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  • 7
    Electronic Resource
    Electronic Resource
    Polypeptides controlling hematopoietic cell development and activation (1989)
    Springer
    Annals of hematology 58 (1989), S. 117-128 
    Details
    ISSN: 1432-0584
    Keywords: Hematopoietic growth factors ; In vitro effects ; Progenitor cells ; Mature end-cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Recombinant DNA technology has been central in answering some of the most relevant questions in the research of regulation of the functional status of hematopoietic progenitor cells and their progeny. This leading article will focuse on recent results that have emerged from studies utilizing recombinant molecules that control hematopoietic blood cell development and activation. The following features will be detailed: The molecular and biological characteristics and biochemistry of hematopoietic growth factors, synergizing factors and releasing factors, their role in the regulation of hematopoiesis and activation of normal and leukemic cells, their cellular sources, and regulation of production.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00320430
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  • 8
    Electronic Resource
    Electronic Resource
    Polypeptides controlling hematopoietic blood cell development and activation (1989)
    Springer
    Annals of hematology 58 (1989), S. 173-179 
    Details
    ISSN: 1432-0584
    Keywords: Hematopoietic growth factors ; Clinical application
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Colony-stimulating factors (CSFs) have entered the clinical arena. Several investigators have explored, in first clinical phase I studies, different routes of administration to define the optimum biological dose, maximum tolerated dose, toxicity, and pharmacokinetics of these reagents. It has been demonstrated that recombinant human (rh) granulocyte-macrophage CSF (GM-CSF) and granulocyte CSF (G-CSF) can be safely administered over a broad dose range to increase number of circulating granulocytes in man. More recently, GM-CSF and G-CSF have been involved in phase Ib/II studies to assess the granulopoietic responses of patients with granulocytopenia due to various underlying disease states including myelodysplastic syndrome, aplastic anemia, cyclic neutropenia, Kostmann's syndrome, and the acquired immuno-deficiency syndrome. Both factors were also investigated with respect to their potential to prevent chemotherapy induced granulocytopenia or to accelerate recovery from that condition. The short-term effects of rh GM-CSF after autologous bone marrow transplantation for various solid tumors and lymphoid malignancies were assessed as well. In this article we will focus on recent results that have emerged from in vivo studies utilizing CSFs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00320769
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  • 9
    Electronic Resource
    Electronic Resource
    Standard- and high-dose etoposide, ifosfamide, carboplatin, and epirubicin in 100 patients with small-cell lung cancer: A mature follow-up report (1999)
    Springer
    Annals of oncology 10 (1999), S. 561-567 
    Details
    ISSN: 1569-8041
    Keywords: chemotherapy ; hematopoietic growth-factor support ; high-dose chemotherapy ; peripheral blood stem-cell transplantation ; small-cell lung cancer ; treatment toxicity and mortality
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: We conducted a phase I–II trial to assess the feasibility and activity of a combination chemotherapy regimen with etoposide, ifosfamide, cisplatin or carboplatin, and epirubicin in limited-disease (LD, stages I–IIIB) and extensive-stage (ED, stage IV) small-cell lung cancer (SCLC). Patients and methods: Standard-dose chemotherapy (SDC) consisting of etoposide (500 mg/m2), ifosfamide (4000 mg/m2), cisplatin (50 mg/m2) and epirubicin (50 mg/m2) (VIP-E), followed by granulocyte colony-stimulating factor (G-CSF), was given to 100 patients with SCLC. Thirty patients with qualifying responses to VIP-E proceeded to high-dose chemotherapy (HDC) with autologous peripheral blood stem-cell transplantation (PBSCT) after etoposide (1,500 mg/m2), ifosfamide (12,000 mg/m2), carboplatin (750 mg/m2) and epirubicin (150 mg/m2) (VIC-E) conditioning. Results of standard-dose VIP-E: Ninety-seven patients were evaluable for response. The objective response rate was 81% in LD SCLC (33% CR, 48% PR; excluding patients in surgical CR) and 77% in ED SCLC (18% CR, 58% PR). The treatment-related mortality (TRM) of SDC was 2%. Two additional patients in CR from their SCLC developed secondary non-small-cell lung cancers (NSCLC), and both were cured by surgery. The median survival was 19 months in LD SCLC and 6 months in ED SCLC. The five-year survivals were 36% in LD and 0% in ED SCLC. Results of high-dose VIC-E: HDC was feasible in 16% of ED-, and 58% of LD-patients. All HDC patients (n = 30) improved or maintained prior responses. Four patients died of early treatment-related complications (TRM 13%). Two additional patients in CR from their SCLC developed secondary malignancies (esophageal cancer, secondary chronic myelogenous leukemia). The median survivals were 26 months in LD SCLC, and 8 months in ED SCLC. The five-year survival was 50% in LD and 0% in ED SCLC. Conclusions: Despite high response rates, survival after VIP-E SDC and VIC-E HDC in patients with ED SCLC is not superior to that achieved with less toxic traditional regimens. The high five-year survival rates achieved with these protocols in LD SCLC probably reflect both patient selection (high proportion of patients with prior surgical resection) and the high activity of our chemotherapy regimen in combination with radiotherapy. A study comparing protocols using simultaneous radiation therapy and chemotherapy, and other dose-escalated forms of SDC with HDC is needed to further define the role of this treatment modality in SCLC. Given the high rate of secondary malignancies observed in patients in CR 〉2 years in our study, close follow-up and early treatment of these neoplasms may contribute to maintaining overall survival in patients with SCLC.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1026453922931
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